08.17 The paradoxical effects of tnf-α on osteoblastogenesis

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Abstract

Objective

The full effect of anti-TNF therapy on new bone formation is still in debate in spondylitis fields. We sought to obtain circulating osteoblast-lineage cells in peripheral blood from ankylosing spondylitis (AS) patients and healthy control subjects, and to evaluate the effect of TNF-α on osteoblastogenesis in patients with AS before and after infliximab therapy.

Methods

Sixteen male patients with AS slated for infliximab therapy and 19 controls were recruited. We cultured osteoblast-lineage cells from peripheral blood and measured the optical density of their alizarin red S staining. We also measured serum P1NP (procollagen type 1 N-terminal propeptide) as an early osteoblast differentiation marker, osteocalcin as a late osteoblast differentiation marker, and inflammatory markers.

Results

There were significantly more circulating osteoblast-lineage cells in patients than in controls. The number of circulating osteoblast-lineage cells and optical density of Alizarin S staining decreased 14 weeks after infliximab therapy (p=0.028); serum level of P1NP decreased, but that of osteocalcin increased (p=0.002 and 0.007 respectively).

Conclusion

Our data reveals first, TNF-α stimulates osteoblastogenesis before infliximab therapy in patients with AS; second, infliximab therapy resolves early inflammation, but allows mature osteoblast differentiation in late inflammation. The culture of osteoblast-lineage cells in peripheral blood may be a candidate for a new modality with which study spondylitis and other autoimmune diseases.

Funding

This study is supported by grant from the National Research Foundation of Korea (NRF-2014R1A1A2058007) to Dr. S-R Kwon

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